A key function of the gustatory system is to detect nutrients, toxins and indicators of spoilage, thus providing critical information to the animal about the quality and nutritional value of food before it is ingested. The ability to detect and discriminate taste stimuli is essential for health and survival, and can drive ingestive behaviors. Therefore, physiological mechanisms that modulate taste function in the context of nutritional needs and metabolic status could optimize ingestive decisions and directly impact human health. Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the physiological mechanisms that link taste function and metabolism are poorly understood. Recent findings from our laboratory and others suggest that the gustatory and gastrointestinal systems utilize a common molecular toolkit of receptors, signaling molecules and hormones to detect nutrients and other chemicals. This is consistent with a role for taste function in the maintenance of metabolic homeostasis and suggests that sensory function may be modulated in the context of metabolic status. A greater understanding of the interactions between metabolic hormones and the gustatory sensory apparatus would have important consequences for understanding the etiology of metabolic disease. This project will investigate the interactions between taste and hormonal systems in three Aims. In Aim 1, we will examine the contribution of taste receptors and taste receptor variants to the maintenance of glucose homeostasis. In Aim 2, we will characterize the role of two hormones expressed in taste cells and in the digestive system, glucagon-like peptide-1 (GLP-1) and glucagon, in the modulation of taste sensitivity. In Aim 3, we will examine the ability of GLP-1, glucagon and another hormone, leptin, to influence each other's effects on taste function. Together, these studies will offer important new insights into the interplay between taste, nutrition and metabolism and could have broad implications for metabolic diseases such as obesity, Type 2 diabetes mellitus, and the metabolic syndrome. PUBLIC HEALTH RELEVANCE Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the physiological mechanisms that link taste function and metabolism are poorly understood. Recent findings from our laboratory and others suggest that taste is important for the maintenance of metabolic homeostasis and that taste function may be modulated in the context of metabolic status. The proposed studies will investigate the interactions between taste and hormonal systems, providing important new insights into the interplay between taste, nutrition and metabolism that could have broad implications for metabolic diseases such as obesity, Type 2 diabetes mellitus, and the metabolic syndrome.